Resolor (Resolor)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substancePrukalopridePrukalopride
Similar drugsTo uncover
  • Resolor
    pills inwards 
    Johnson & Johnson, LLC     Russia
    • Dosage form: & nbspfilm-coated tablets
    Composition:

    Tablets, film-coated, 1 mg:

    active ingredient: prukalopride succinate 1.321 mg in terms of 1 mg prucalopride;

    auxiliary substances: Icore tablet: lactose monohydrate 149.969 mg, microcrystalline cellulose 27.00 mg, silicon dioxide colloidal 0.36 mg, magnesium stearate 1.35 mg, a white-1 6,00 mg; fromof white-1 film coating in percent by weight: gand promromethosis 6 cp 40%, titanium dioxide 24%, macrogol 3000 8%, triacetin 6%, lactose monohydrate 22%.

    Tablets, film-coated, 2 mg:

    active ingredient: prukalopride succinate 2.642 mg in terms of 2 mg prucalopride;

    Excipients: Icore tablet: lactose monohydrate 165,458 mg, microcrystalline cellulose 30.00 mg, silicon dioxide colloidal 0.40 mg, magnesium stearate 1.50 mg, film coating pink 7.00 mg; fromLeave a film coating of pink in percentage by weight: gand promromethosis 6 cp 40%, iron dye oxide red (E172) 0.09%, titanium dioxide 23,88%, macrogol 3000 8%, triacetin 6%, lactose monohydrate 22%, indigo carmine (E132) 0,02%, ferric oxide yellow oxide (E172) 0,01%.

    Description:

    Tablets, film-coated 1 mg: tobifid biconvex tablets, covered with a film coating of white or almost white color.On one side - engraving "PRU 1 ".The cross section of the tablet core is white or almost white.

    Tablets, film-coated, 2 mg: tobifurcated biconvex tablets covered with a pink film membrane. On one side - engraving "PRU 2 ".The cross section of the tablet core is white or almost white.

    Pharmacotherapeutic group:serotonin receptor stimulant
    ATX: & nbsp

    A.06.A.X.05   Prukalopride

    Pharmacodynamics:

    Prukalopride is a dihydrobenzofurancarboxamide that enhances intestinal motility. Prukalopride is a selective, high affinity agonist 5NT4-serotonin receptors, which, most likely, explains its effect on intestinal motility. Binding to other types of receptors in vitro It was observed only at concentrations of the substance exceeding its affinity for NT4receptors at least 150 times.

    Pharmacokinetics:

    Suction

    Prukalopride is rapidly absorbed; after a single oral dose of 2 mg maximum concentration (CmOh) is achieved through 2-3 hours. Absolute bioavailability after oral intake exceeds 90%. The intake of the drug during meals does not affect the bioavailability.

    Distribution

    Prukalopride is distributed throughout the body, the volume of distribution in the equilibrium condition (Vdss) is 567 liters. Binding to plasma proteins is approximately 30%.

    Metabolism

    Metabolism of the drug in the human liver in vitro proceeds very slowly, and only a small amount of metabolites is formed. After oral ingestion by a human 14C-labeled prukalopride in urine and feces are found in small amounts 8 metabolites. The main metabolite (R107504, formed by O-demethylation of prucalopride and oxidation of the alcohol to carboxylic acid) is less than 4% injected dose of the drug. As studies with a radioactive label showed, about 85% of the drug remains unchanged; metabolite R107504 is present in the plasma in small amounts.

    Excretion

    Most of the orally taken dose of the active ingredient is excreted unchanged (approximately 60% by the kidneys and at least 6% with feces). The excretion of unchanged prucalopride by the kidneys includes passive filtration and active secretion. The clearance of prucalopride from plasma is an average of 317 ml / min, the final half-life is about 1 day. The equilibrium state is achieved after 3-4 days of taking the drug, and when taking prucalopride in a dose 2 mg 1 once a day, the minimum and maximum plasma concentrations in the equilibrium state are 2.5 and 7 ng / ml, respectively. When you take 1 time a day, the ratio k the drug ranges from 1.9 to 2.3. The pharmacokinetics of prucalopride linearly depend on the dose in the range up to 20 mg / day. With long-term use of the drug once a day, its pharmacokinetics does not depend on the duration of administration.

    Specials categories patients

    Population pharmacokinetics

    Population pharmacokinetics analysis showed that the total clearance of prucalopride correlates with creatinine clearance and does not depend on the age, body weight, sex or race of patients.

    Elderly patients

    When taking the drug by elderly patients at a dose of 1 mg once a day, the maximum concentration of prucalopride in the blood plasma (CmOh) and the area under the concentration-time curve (AUC) were 26% and 28%, respectively, more than in young patients. This difference may be due to the weakening of kidney function in the elderly.

    Impaired renal function

    Compared with patients with normal renal function, in patients with a weak (creatinine clearance 50-79 ml / min) and moderately pronounced (QC 25-49 ml / min) impaired renal function, the concentration of prucalopride in the blood plasma after a single dose of 2 mg was increased by 25% and 51% respectively.In patients with severe renal dysfunction (creatinine clearance less than 24 ml / min), the concentration of prucalopride in blood plasma was 2.3 times higher than in healthy people.

    Impaired liver function

    About 35% of prucalopril is excreted extrarenally, therefore, a violation of liver function is unlikely to clinically significantly change the pharmacokinetics of the drug.

    Children

    After a single oral administration of prucalopride at a dose of 0.03 mg / kg in children aged 4-12 years maximum concentration (CmOh) of the drug was the same as after taking the drug by adults in a dose 2 mg, and the area under the concentration-time curve (AUC) of the unbound fraction of the drug was 30-40% less than in adults, and did not depend on the age of the children. The average half-life of the drug in the terminal phase is approximately 19 hours in children (range 11.6-26.8 hours).

    Indications:

    Resolor is intended for symptomatic therapy of chronic constipation in women whose laxatives have not provided sufficient effect in eliminating symptoms.

    Contraindications:

    - Hypersensitivity to the active ingredient or any auxiliary substance;

    - renal dysfunction requiring dialysis;

    - perforation or intestinal obstruction due to anatomical or functional disorders of the intestinal wall, mechanical intestinal obstruction, severe intestinal inflammation, eg Crohn's disease, ulcerative colitis and toxic megacolon / megarectum;

    - congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

    Carefully:

    The use of the drug in patients with severe and clinically unstable concomitant diseases (liver, lung, cardiovascular, neurological, endocrine diseases, psychiatric disorders, oncological diseases, AIDS) has not been studied. Care should be taken when prescribing Resolor to patients with such diseases. In particular, caution should be used in patients with cardiac arrhythmia or ischemic heart disease in history.

    Pregnancy and lactation:

    Pregnancy

    The experience with prucalopride during pregnancy is limited. In clinical trials, cases of miscarriage have been recorded, although, given the presence of other risk factors, the association of these phenomena with prucalopride remains unproven.Studies in animals showed no direct or indirect adverse effects on the course of pregnancy, embryo / fetal development, childbirth and postnatal development of offspring. The drug Resolor is not recommended for use during pregnancy. During the treatment with prukalopride, women, capable of childbearing, Adequate methods of contraception should be used.

    Lactation period

    Prukalopride is excreted in breast milk, but when applied in therapeutic doses, the drug is unlikely to affect newborns / infants. Due to the lack of data on the use of lactating mothers, the drug is not recommended for use during breastfeeding.

    Ability to conceive

    Studies in animals have not revealed any effect of the drug on the fertility of males and females.

    Dosing and Administration:

    The drug is taken orally, regardless of food intake, at any time of the day.

    Adults: 2 mg once a day.

    Elderly (over 65 years of age): begin with 1 mg once a day, if necessary, increase the dose to 2 mg 1 once a day.

    Children and adolescents: Resolor is not recommended for use in children and adolescents under the age of 18 years.

    Patients with impaired renal function: with severe renal dysfunction (speed glomerular filtration less than 30 ml / min / 1.73 m2) the dose is 1 mg 1 time per day. For patients with mild and moderate impairment of renal function, dose adjustment is not required.

    Patients with impaired hepatic function: with a severe violation of liver function (class C according to Child-Pugh), the dose is 1 mg 1 time per day. For patients with a mild and moderately severe impairment of liver function, dose adjustment is not required.

    Due to the specific mechanism of action of prucalopride (stimulation of intestinal motility), an increase in the daily dose of more 2 mg is unlikely to lead to an enhanced effect. If taking prucalopride once a day for 4 weeks does not have an effect, the patient should be re-examined and the expediency of continuing treatment should be determined.

    Side effects:

    The most frequent adverse reactions with the use of the Resolor drug were headache and undesirable reactions from the gastrointestinal tract (abdominal pain, nausea, diarrhea), each of which was observed in approximately 20% of patients! Unwanted reactions developed mainly at the beginning of treatment and usually disappeared after a few days, without requiring the withdrawal of treatment. Other adverse reactions were observed episodically.Most adverse adverse reactions were of mild to moderate severity.

    With the recommended dose of prukalopride 2 mg in clinical studies, the following undesirable reactions are recorded, whose frequency is indicated as:

    Very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), including isolated cases.

    From the central nervous system:

    Very often: headache;

    Often: dizziness;

    Infrequently: tremor.

    From the cardiovascular system:

    Infrequent: palpitations.

    From the gastrointestinal tract:

    Very often: nausea, diarrhea, abdominal pain;

    Often: vomiting, indigestion, rectal bleeding, flatulence, pathological intestinal noises.

    Infrequently: anorexia.

    From the genitourinary system

    Often: pollakiuria.

    Are common

    Often: weakness;

    Infrequently: fever, poor health.

    Overdose:A study involving healthy volunteers showed that prukalopride well tolerated by increasing the dose to 20 mg 1 once a day (in 10 times more than the recommended therapeutic dose). Overdose can lead to symptoms caused by an increase in known side effects of the drug, including headache, nausea and diarrhea.
    Specific antidote for the drug Resolor does not exist. In case of an overdose, symptomatic and supportive therapy should be carried out if necessary. A large loss of fluid due to diarrhea or vomiting may require correction of electrolyte imbalance.
    Interaction:

    Data in vitro indicate a weak ability of prukalopride to interact, and in therapeutic concentrations, it hardly affects the metabolism of concomitant medications carried out by the enzymes of the cytochrome system. Although prukalopride can weakly bind to P-glycoprotein (P-GP), at clinically significant concentrations it does not inhibit activity (P-GP).

    Powerful inhibitor CYP3A4 and P-glycoprotein ketoconazole in a dose of 200 mg twice a day increased AUC (area under the concentration-time curve) of prucalopride by approximately 40%. This effect is too small to be clinically significant, and is most likely related to the suppression of the pr-glycoprotein-active prucalopride in the kidneys. The same interaction as with ketoconazole om, can be observed with other active inhibitors of the P-glycoprotein, for example, verapamil, cyclosporin A and quinidine. Prukalopride, rather in total, is also transported in the kidney and other vectors. Theoretically, suppression of the activity of all carriers participating in active secretion of prucalopride in the kidneys (including P-glycoprotein) can increase the level of its systemic exposure by 75%.

    Studies involving healthy volunteers showed no clinically significant effect of prucalopride on the pharmacokinetics of warfarin, digoxin, ethyl alcohol, and paroxetine. With simultaneous application of prucalopride and erythromycin, the concentration of the latter in the blood plasma is increased by 30%. The mechanism of this interaction is not completely clear, but the available data indicate that it is most likely not the result of direct action of prucalopride, but a consequence of the high variability of the pharmacokinetics of erythromycin itself.

    Probenecid, cimetidine, erythromycin and paroxetine in therapeutic doses did not affect the pharmacokinetics of prucalopride.

    The drug Resolor should be used with caution at the same time with drugs that can lengthen the interval QTc.

    Atropine-like substances can weaken the effects of prucalopride mediated through HT receptors4.

    No interaction was found with food.

    Special instructions:

    The main way of deducing prukalopride is through the kidneys. For patients with severe renal dysfunction, the recommended dose is 1 mg.

    Severe diarrhea can reduce the effectiveness of oral contraceptives, and additional methods of contraception are recommended to prevent a decrease in the effectiveness of oral contraceptives (see instructions for the use of oral contraceptives).

    Violation of the function of the liver is unlikely to have a clinically significant effect on the metabolism and the level of systemic exposure of prucalopride in humans. Data on the use of the drug in patients with mild, moderate or severe liver dysfunction no, therefore, a lower dose is recommended for patients with severe impairment of liver function.

    The drug contains lactose monohydrate, so the drug can not be taken by patients with congenital deficiency of lactase, lactose intolerance or glucose-galactose malabsorption.

    For prucalopride, neither the rebound phenomenon nor the development of dependence was detected.

    The study of the effect of prucalopride on the interval QT in therapeutic (2 mg) and supra-therapeutic (10 mg) dosages did not show significant differences compared to placebo for the values ​​of the interval QT. Frequency of adverse events associated with the interval QT, and ventricular arrhythmias were low and comparable to those of placebo.

    Effect on the ability to drive transp. cf. and fur:

    Studies of the effect of prucalopride on the ability to drive and move vehicles have not been carried out. In some cases, the use of Resolor has been associated with the development of dizziness and weakness, especially in the early days of treatment, which may affect the ability to drive and move vehicles.

    Form release / dosage:

    Tablets, film-coated, 1 mg and 2 mg.

    Packaging:

    7 tablets per blister from AL / AL.

    By 1, 2, 3, 4, 5, 6, 7 or 8 blisters together with instructions for use in a cardboard pack.

    Storage conditions:

    Store in original packaging at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Keep in original packaging to protect from moisture.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001413
    Date of registration:11.01.2012
    The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspJohnson & Johnson LLC Johnson & Johnson LLC Russia
    Information update date: & nbsp10.09.2015
    Illustrated instructions
      Instructions
      Up